Roche P A, Cresswell P
Department of Microbiology and Immunology, Duke University Medical Center, Durham, NC 27710.
Proc Natl Acad Sci U S A. 1991 Apr 15;88(8):3150-4. doi: 10.1073/pnas.88.8.3150.
HLA-DR molecules are heterodimeric transmembrane glycoproteins that associate intracellularly with a polypeptide known as the invariant (I) chain. Shortly before expression of the HLA-DR alpha beta dimer on the cell surface, however, the I chain is removed from the intracellular alpha beta I complex by a mechanism thought to involve proteolysis. In this report, we show that treatment of purified alpha beta I with the cysteine proteinase cathepsin B results in the specific proteolysis of the HLA-DR-associated I chain in vitro. As a consequence of this, the I chain is removed and free alpha beta dimers are released from alpha beta I. Although alpha beta I fails to bind an immunogenic peptide, the released alpha beta dimers acquire the ability to bind the peptide after proteolysis of the I chain. These results suggest that the I chain inhibits immunogenic peptide binding to alpha beta I early during intracellular transport and demonstrate that proteolysis is likely to be the in vivo mechanism of I chain removal.
HLA - DR分子是异二聚体跨膜糖蛋白，在细胞内与一种称为恒定（I）链的多肽结合。然而，就在HLA - DRαβ二聚体在细胞表面表达前不久，I链通过一种被认为涉及蛋白水解的机制从细胞内αβI复合物中被去除。在本报告中，我们表明用半胱氨酸蛋白酶组织蛋白酶B处理纯化的αβI会导致体外HLA - DR相关I链的特异性蛋白水解。由此，I链被去除，游离的αβ二聚体从αβI中释放出来。尽管αβI不能结合免疫原性肽，但在I链蛋白水解后，释放的αβ二聚体获得了结合该肽的能力。这些结果表明，I链在细胞内转运早期抑制免疫原性肽与αβI的结合，并证明蛋白水解很可能是I链在体内被去除的机制。
